The objective of this proposal is to explore the development of a detector capable of detecting with high sensitivity and high spatial resolution optical photons in the visible wavelength as well as high energy photons, such as those emitted during positron annihilation. We further propose to use this new detector to construct a prototype imaging system that will be capable to non-invasively and repeatedly image small animal models in-vivo for the presence of either Positron Emission Tomography (PET) or optical signals. We will call this new device optical PET (OPET). Our interest is in ultimately using this technology as a tool that will enable translational research by bridging optical imaging at the cellular and small animal level, to microPET and on to human PET applications in the clinic. While we develop this technology for this translational research application, we expect that a multitude of other applications will manifest themselves from the photon counting nature of operation and high sensitivity of this device. We have previously developed the second generation of the high-resolution microPET scanners, and we plan to use a similar detector configuration for the detection of both optical and PET signals. This novel device therefore will use the same physical detector, and will completely eliminate the need for software image registration between PET and optical images. Specifically in this proposal, we plan to investigate different position sensitive and multi-channel imaging photodetectors, ranging from multi-channel photomultiplier tubes with different photocathode materials, to silicone based Avalanche Photo Diode (APD) detectors. We will also study methods of optimizing and maximizing the collection of light photons from scintillation events as well as optical signals. Finally we will build a prototype system based on a small number of detectors, and we will acquire the initial optical/PET studies. The developed imaging system will be a new tool dedicated to imaging small animals and will have high sensitivity and spatial resolution for both signals. We expect it to have optical signal sensitivity equivalent to state of the art optical imaging systems, PET absolute system sensitivity of state of the art commercial systems (on the order of 2%), and spatial resolution on the order of 2 mm. Furthermore, this imaging system will be of reduced cost, due to its field of view customized to the application of small animal imaging.